Biophysical Properties of the Extracellular Matrix in Cancer: Insights Into Immunotherapy

The tumor microenvironment, especially the extracellular matrix (ECM), plays a critical role in cancer initiation and progression, although its underlying mechanisms remain incompletely understood. Conventional therapies (such as chemotherapy, surgery, and radiotherapy) often produce unsatisfactory outcomes. Immunotherapy, while showing limited clinical success to date, holds considerable promise. Growing evidence indicates that the biophysical properties of the ECM interact with immune cells, contributing to mechanisms of immunotherapy resistance in cancer. Alterations in these ECM properties can impair immune cell infiltration and function, thereby diminishing the effectiveness of immunotherapeutic approaches. This review explores how the biophysical features of the ECM and their crosstalk with tumor immune evasion pathways highlight the potential of ECM-targeted immunotherapy as an innovative strategy for cancer treatment.